The objective of the proposed program is to gain an understanding of the molecular basis of tissue specific intercellular adhesion. Attention is focused on the adhesive properties of embryonic, adult, regenerating, and neoplastic liver cells from chick, rat, and mouse. The adhesive specificity of these cells is being studied using a specific cell adhesion assay (collecting aggregate assay). The properties and specificity of this assay procedure are being studied in detail. Refinement of existing assay procedures may lead to methods for studying the more subtle cell type interactions underlying histogenic organization. Other studies are directed at the identification, isolation, and characterization of the tissue specific cell ligands responsible for adhesive specificity. Liver cell plasma membranes are also being isolated to gain insight into the functional integration of these molecules within this organelle. Elucidation of the chemical basis of ligand interactions (protein:protein, protein:carbohydrate) underlying cell-to-cell interactions involved in morphogenesis, differentiation, and tissue homeostasis is the long range goal of this program. The potential regulation of intercellular adhesion during development, neoplastic alterations, and mitosis is being studied. The role of cyclic AMP and cyclic GMP in such regulation will be determined. The possibility that hepatoma cells escape "social" restrictions (regulation of division, movement, differentiation, and adhesion properties) will be examined. The study of tissue specific adhesive behavior of cells represents an approach to an analysis of the complex problem of tissue homeostasis. The "unsocial" behavior of neoplastic cells is a fundamental property, but probably represents secondary alterations of the primary events of oncogenesis. Nevertheless, an analysis of intercellular adhesion may yield an understanding of many important phenomena, such as the underlying basis for metastases.